The B cell maturation antigen (BCMA) is dispensable for long-lived plasma cell survival

Survival of antibody-secreting plasma cells is a prerequisite to establish long-lasting humoral immune protection. The B cell maturation antigen (BCMA) has been proposed to promote APRIL-mediated survival signals in plasma cells. However, the extensive shedding of murine BCMA from the plasma cell surface raises doubts about its ability to function as a signaling receptor. To unequivocally establish whether BCMA is required for long-lived plasma cell survival, we established two independent BCMA-deficient mouse lines and analyzed the survival of antigen-specific plasma cells after immunization. In contrast to published data, we found comparable numbers of long-lived antigen-specific plasma cells after primary and secondary protein and mRNA immunizations in BCMA-deficient mice. In addition, wildtype and BCMA-deficient plasma cells showed comparable transcriptome profiles with no indication for reduced survival signaling. Interestingly, total plasma cell numbers were increased after boost immunization in bone marrow and mesenteric lymph nodes of BCMA-deficient mice. Therefore, BCMA has no intrinsic role in maintaining long-lived plasma cells. We propose a function of BCMA limited to acting as a soluble decoy receptor for APRIL and fine-tuneing the size of the plasma cell population by limiting the availability of survival factors. This finding removes a piece of the puzzle of the mechanisms that contribute to long-lived plasma cell survival. Comparative gene expression profiling analysis of RNA-seq data for splenic and bone marrow plasma cells from BCMA (Tnfrsf17) WT/KO mice under steady state conditions and after Spikevax (mRNA-1273) immunization